Autosomal recessive intermediate Charcot-Marie-Tooth disease type B

Autosomal recessive intermediate Charcot-Marie-Tooth disease type B (RI-CMTB, also known as CMTRIB) is a rare inherited peripheral neuropathy caused by mutations in the KARS1 gene, which encodes lysyl-tRNA synthetase. This enzyme plays a critical role in protein synthesis, and its dysfunction leads to progressive damage to both motor and sensory peripheral nerves. The term 'intermediate' refers to nerve conduction velocities that fall between the demyelinating and axonal ranges (typically 25–45 m/s), indicating features of both nerve fiber demyelination and axonal degeneration. The disease primarily affects the peripheral nervous system, leading to progressive distal muscle weakness and atrophy, particularly in the lower limbs, resulting in difficulty walking and foot deformities such as pes cavus (high-arched feet) and hammer toes. Sensory impairment, including reduced sensation in the hands and feet, is also common. Onset typically occurs in childhood or adolescence. Some patients may also develop additional neurological features, including developmental delay, hearing loss, or mild central nervous system involvement, reflecting the broader role of KARS1 in cellular function. There is currently no cure or disease-specific treatment for RI-CMTB. Management is supportive and multidisciplinary, focusing on physical therapy and rehabilitation to maintain mobility, orthotic devices to assist with gait, and orthopedic surgery when needed for skeletal deformities. Pain management and occupational therapy may also be beneficial. Genetic counseling is recommended for affected families. Research into potential targeted therapies is ongoing but remains in early stages.

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